Conducting chemical reactions on the microscopic scale in a miniature analytical device, while being able to precisely vary reaction parameters such as concentration and temperature has been made possible by trends in microfluidics and combinatorial chemistry. Such control requires thermal regulation using a localized heat source on the miniature analytical device.
The term “miniature analytical device” refers to a device for conducting chemical and biological analytical tests (“assays”) on a smaller scale as related to bench-top analytical equipment. Because such devices are small and light weight, they can be portable as well as modular with disposable and reusable portions. The portability of such devices makes it possible to carry out such reactions near the patient, at the point of care, rather than in the laboratory.
The term “localized heat source” refers to a source of heat which is proximate to the substance to be heated. Such a source can comprise multiple point sources of heat. One particular area in which being able to carry out chemical and biological reactions on a miniature device in the field has great importance is the area of medical diagnostics of bodily fluids such as blood.
Medical diagnostics of bodily fluids can involve several assays using a variety of assay elements. The term “reactant” refers to chemicals involved in a synthetic reaction, or assay elements such as body fluid samples (such as blood), washes, and reagent chemicals. Sensing methods for blood metabolites such as pO2, pCO2, Na+, Ca++, K+, glucose or clinical parameters such as blood pH, hematocrit, and coagulation and hemoglobin factors include electrochemical, chemiluminescence, optical, electrical, mechanical and other methods.
The home-care or self-analysis by patients has been facilitated by miniature analytical devices that can analyze body fluids. Many POC tests are performed using capillary whole blood. Typically, a drop of blood for analysis is obtained by making a small incision in the fingertip or forearm, creating a small wound, which generates a small blood droplet on the surface of the skin. Moving tests closer to the patient's side by using miniature analytical devices, improves both the testing process and the clinical data information management, which in turn has a dramatic impact on both patient outcomes and costs to the health care system.
Some of the desired biochemical tests require a specified and stabilized temperature for accurate and reportable measurements. Prior solutions to the problem of controlled temperature included large instruments with substantial temperature-controlled zones that required significant electrical power to provide heating.
The term “heating” refers to adding heat to a substance to raise its temperature and removing heat from a substance to reduce its temperature. The term “thermal regulation” refers to modifying heating to increase, decrease, or maintain the temperature of a substance to a desired temperature.
Thermal regulation of reactants or assay elements can be achieved through bulk heating of the cartridge using heaters such as electrical resistance heaters, Peltier heating and cooling cells, air heaters, or infrared heaters. These bulk-heating systems are usually large, and have generous energy supplies. POC devices require smaller volumes than bench-top systems. POC device volumes range between 1×10−1 and 1×103 microliters. More specifically, a POC diagnostic device can heat volumes of 1-5 micro liters of assay elements, such as a blood sample, and/or 100-500 micro liters of assay elements, such as reagents. Restricting the volume to be heated to the temperature-controlled zones reduces the amount of heat required and facilitates localized heating.
For a POC device to be truly portable, power management is a critical issue. One method of limiting power usage is to localize heating to only those zones where heating is necessary. Localized heating provides lower power consumption and more rapid attainment of a specified reaction temperature. Such a localized approach to heating has the added benefit of minimizing the cost of manufacturing the disposable cartridge for diagnostic analysis. The localized heating elements needed for the rapid transmission of heat and the regulation of temperature can be located on the POC device and the assay elements to be heated can be located on the disposable cartridge. Such efficiencies in power usage can save battery life.
There have been attempts at designing thermal regulation devices for miniaturized reaction chambers for synthetic and diagnostic applications such as PCR amplification, nucleic acid hybridization, chemical labeling, and nucleic acid fragmentation. These attempts have focused on bulk resistive heating. Bulk resistive heating requires direct contact between the POC device and the cartridge with the reactance. Bulk resistive heating is inefficient and slow compared to localized heating because it heats the surrounding environment as it heats the assay elements contained within the cartridge. Bulk resistive heating increases the time it takes to increase the temperature of the reactance because the cartridge must be heated to the desired temperature. Localized heating shortens the distance over which external heating occurs, bypasses the cartridge with radiation directed to the reactance, or heats from within the reactance.
It is accordingly a primary object of the invention to localize heating to specific temperature-controlled zones in a cartridge using electromagnetic radiation, internal heat, or external heat. The advantages are that such localized heating does not require direct contact with the entire cartridge. The localized energy provided by these heat sources can be easily and accurately manipulated so that the amount of energy directed towards portions of the cartridge can be finely tuned and controlled so that the desired temperature is rapidly achieved and maintained. Heating by localized energy mainly affects the reactance themselves, rather than the entire cartridge and/or the environment.